Objective To collect and summarize long-term complications of glucocorticoid (GC) in treatment of Diamond-Blackfan anemia (DBA).Methods A total of 17 DBA patients,treated with GC more than 1 year from December 2009 to November 2012 in Being Children's Hospital,Capital Medical University,were retrospectively investigated.The data of general information,drug treatment,treatment response,height and body mass in different therapy periods,and therapy related adverse reaction were collected.The data entry and the statistical analysis were performed using SPSS 16.0 software.Results Seventeen cases which fulfilled the research criteria were enrolled.The 58.8 percent of cases (10/17) began GC therapy from the age younger than 6 months.The 76.4 percent of the cases (14/17) started prednisone therapy with the dosage ≥2 mg/(kg · d),and the median time of maintenance therapy with this dosage was 2 months (1-5 months).The median time of prednisone dosage greater than 0.5 mg/(kg · d) was 6 months (3-48 months).Patients were divided into 2 groups at the beginning of therapy according to whether their age was younger or older than 6 months.The median height of younger age group was-1.0 SD (-3.5-1.0 SD) of corresponded age-sex-standard height at the beginning of prednisone therapy,and was dropped to-3.5 SD (-3.5--2.0SD)afterhalfyeartreatment.For older age group,it was0.0 SD(-1.5-2.0 SD)and-0.5 SD (-1.5-0.5 SD) respectively.During the therapy,there were 1 fracture,2 measles pneumonia,3 pneumonia,3 hirsuitisms,5 thrushes,and 12 central obesity cases.Conclusions GC related adverse reaction might appear when applying prednisone for the treatment of DBA in long term.It was suggested that GC therapy should start after 6 months old if possible,and the duration of 0.5 mg/(kg · d) GC treatment should be reduced as short as possible.

Objective To investigate the impact of auto and allogenic mesenchymal stem cells (MSC) transplantation on hematopoietic reconstitution. Methods MSC from auto, donor bone marrow or embryonic tissue were cultured and expanded in vitro in the serum culture system. Five patients received hematopoietic stem cell transplantation (HSCT) were investigated. Case 1 of systemic lupus erythematosus and Case 2 of non-hodgkin' s lymphoma (NHL) received auto MSC transplant before auto-HSCT. Case 3 of paroxysmal nocturnal hemoglobinuria received HLA-identical allogenic MSC transplant before HLA-identical allo-HSCT.Case 4 of chronic myelocytic leukemia and Case 5 of NHL had delayed hematopoietic reconstitution (129th and 78th day, respectively) after allo- and auto-HSCT, respectively, and received MSC from embryonic tissue.Results Case 1, 2 and 3 had no manifested side effects after MSC transplantation combined with HSCT.Neutrophil count of case 1, 2, and 3 were over 0.5 ×109/L at 1st, 10th and 10th day, respectively, platelet count were over 20 ×109/L at 1st, 8th and 33th day, respectively, and agranulocytosis at Ost, 7th and 12th day, respectively. The treatment of embryonic tissue MSC transplant was confirmed to fail for Case 4 and 5.Conclusion The time of MSC transplant has a great impact on hematopoietic reconstitution. MSC transplantation and HSCT performed simultaneously can improve hematopoietic reconstitution. However, the impact of MSC on patients with delayed hematopoietic reconstitution after HSCT needs further study.

Objective:This study aims to examine the clinicopathological features, diagnosis, and treatment of pulmonary margin-al zone B-cell lymphoma of mucosa-associated lymphoid tissue (PMZL-MALT). Methods:The clinicopathological features and immu-nohistochemical staining of CD20, CD79a, CD5, CD10, CD23, CyclinD1, and Ki-67 in seven patients with PMZL-MALT were ana-lyzed. Results:These patients, with a median age of 58 years, included three males and four females. Most of the patients suffered from cough, anhelation, and irregular fever. No specific imaging manifestation was observed. Tumor cells were positive for CD19 and CD20 but negative for CD5, CD10, and CyclinD1. The positive rate of Ki-67 was low. Conclusion:PMZL-MALT cases are easily misdiag-nosed because of the absence of specific clinical characteristics and X-ray features. Final diagnosis depends on pathological examina-tions.

Objective To study the current status of catheter - related thrombosis(CRT)in Chinese children through a retrospective analysis of the inpatients in the Department of Medicine,Beijing Children's Hospital Affiliated to Capital Medical University. Methods The clinical data of the inpatients with CRT from November 2010 to November 2013 were collected retrospectively,and the causes,clinical symptoms,diagnosis,treatment and prognosis were ana-lyzed. Results There were 42 cases of children with CRT in Beijing Children's Hospital Affiliated to Capital Medical University. Among the cases,the male to female ratio was 1. 0:0. 5;the median age of onset was 88(2 - 186)months with ﹤ 1 year old counted for 16. 7%(7 / 42 cases)and 13 - 14 years old counted for 11. 9%(5 / 42 cases);the distri-bution differences between the male and the female age were not significant(P = 0. 826). The median time from cathe-terization to CRT onset was 9(1 - 81)days,0 - 10 days after catheterization was the peak of onset(52. 5% ,21 / 40 ca-ses)followed by 10 - 20 days(35. 0% ,14 / 40 cases). The protopathy was usually hematologic tumor,kidney disease or deep fungal infection. Slightly more cases developed CRT on the right side(57. 1% ,24 / 42 cases)than on the left side (38. 1% ,18 / 42 cases). All cases were diagnosed by using B - ultrasound,of whom 28. 6%(12 / 42 cases)were symp-tom - free. After being diagnosed,7. 1%(3 / 42 cases)were treated with conservative methods such as immobilization of the affected limbs and hot compress;7. 1%(3 / 42 cases)had catheter removed;anticoagulant and/ or thrombolytics after catheter removal used in 33. 3% patients(14 / 42 cases). After 1 week,22 cases were reviewed,of whom 54. 5%(12 / 22 cases)had thrombosis reduced(all with intervention),thrombosis growing in 22. 7% patients(5 / 22 cases), and thrombosis did not change in 22. 7% patients(5 / 22 cases). Three cases needed re - catheterization after catheter removal,and all of 3 cases had CRT recurrences(100% ). Conclusions CRT is more common among infants and senior children. CRT usually develops within 20 days after catheterization. Children with hematologic tumor,kidney disease or deep fungal infection are more likely to have CRT. Routine ultrasound test should be conducted to monitor CRT in catheterized children. Once CRT is diagnosed,patients need to be treated with anticoagulants and/ or thrombo-lytics. Catheter should also be removed if necessary. Recatheterization can result in CRT recurrence.

Objective To investigate the distribution of TCR Vβ genealogy and clonal expansion in peripheral blood after infusing mesenchymal stem cells (MSC) in patients with chronic GVHD. Methods The complementarity determining region 3 (CDR3) of 24 TCR Vβ subfamily genes in peripheral blood mononuclear cell from 1 case with cGVHD after allogeneic hematopoietic stem cell transplantation (Allo-HSCT),who were treated with infusing MSC,were amplified using RT-PCR. The blood samples were taken at the first and the fifth day after 1st infusion; and the first day,the 10 th day and the 20 th day after the second infusion of MSC,as well as the MSC infused as control . The products were labelled by fluorescein and then analyzed the CDR3 size with gene scan technique to determine the clonality of T cells. Results There were no expression of TCR Vβ subfamily with the MSC infused and after the 1st day of the first infusion of MSC. Then 3,10,14,10 Vβ subfamilies clones are appeared at the other time points,of which were polyclone and oligoclone predominately. In the same time,the manifestations of cCVHD have been abated. Conclusion MSC played a certain role in reviving the immune function of the patients after Allo-HSCT and mitigating the disease of chronic GVHD. Lineage analysis of TCR Vβ subfamily showed some predominant expression.

Objective: To evaluate the efficacy and safety of imatinib in the treatment of newly diagnosed chronic myeloid leukemia during chronic phase (CML-CP) in children and to analyze the difference of the efficacy and safety between imported original imatinib (Gleevec) and domestic generic imatinib (Xinwei). Methods: Clinical data of 35 children with newly diagnosed CML-CP in Beijing Children′s Hospital from January 2014 to January 2018 were collected, among which 15 cases were treated with the imported original imatinib (original drug group) and 20 cases were treated with the domestic generic imatinib (generic drug group). The hematological, cytogenetic and molecular reactions and safety of the treatments were monitored at months 3, 6 and 12. Chi square test or rank sum test was used for the comparison between two groups. Results: A total of 35 cases were treated for over 3 months, 31 cases were treated for over 6 months and 25 cases were treated for over 12 months. At 3 months, main cytogenetic response was obtained in 15 (100%) cases in the original drug group and 16 (80%) cases in the generic drug group respectively (χ²=3.387, P=0.119). At 6 months, complete cytogenetic response was obtained in 12 (80%) cases in the original drug group and 10 (63%) cases in the generic drug group (χ²=1.435, P=0.390). At 12 months, BCR-ABL^IS ≤ 0.1% was obtained in 11 (92%) cases in the original drug group and 10 (77%) cases in the generic drug group (χ²=1.009, P=0.593). There was no significant difference at all stages (all P>0.05). Hematologic toxicity occurred in 7(20%) cases. The non-hematologic adverse reactions include nausea in 8 (23%) cases, pain in 8 (23%) cases, edema in 6 (17%) cases, emesis in 2 (6%) cases, fever in 2 (6%) cases, weakness in 1 (3%) case, rash in 1 (3%) case. The adverse reactions were easy to control and no drug toxicity related deaths occurred. There was no significant difference in the adverse reactions between original drug group and generic drug group (P>0.05). Conclusions Imatinib had a good efficacy and safety in the early treatment of newly diagnosed CML-CP in children. The efficacy and safety of generic imatinib is similar to that of imported imatinib.

To analyze respectively a case,presented with recurrent petechial and epistaxis after a 2 years history of diabetes mellitus (DM),who was hospitalized in Beijing Children's Hospital Affiliated to Capital Medical University.The clinical manifestation,examination,diagnosis and treatment were recorded.The patient was diagnosed with immune thrombocytopenia (ITP) and DM at the first admission.The initial therapy with gamma globulin didn't show ideal effect.The pediatric specialists from the department of ENT,Hematology/Oncology,Endocrinology,Pharmacy and Immunodeficiency Clinic were invited to discuss the case.The final diagnosis of autoimmune polyglandular syndrome (APS) was made and supplementary steroid treatment was started.But the response of the steroid therapy was poor.Once again with the multidisciplinary consultation,the patient received several schemes of Rituximab under the informed consent.This treatment reached a stable condition for almost 7 years.APS should be considered when DM patient showed the manifestation of other immune organ damages.Rituximab immunosuppressive therapy should be tried when the response to first-line treatment was poor.

Objective To analyze the correlation between genotype,clinical manifestations and treatment response in patients diagnosed as Diamond-Blackfan anemia (DBA) with a clear pathogenic gene mutation.Methods Retrospective investigation was performed of the genetic and clinical data of 42 patients diagnosed as DBA with a definite mutation from December 2009 to October 2017 in Beijing Children's Hospital,Capital Medical University and DBA China group.Results Among 42 patients,no one patient could successfully stop the therapy during the median follow-up time of 40 months (1-136 months).Nucleotide-level mutations or large deletions were identified in 7 ribosomal genes as RPL5,RPL11,RPL35a,RPS17,RPS19,RPS24 and RPS26.The most common gene mutation group was RPS19 (42.9％),followed by RPL11(19.0％),RPS17(11.9％),RPS26(11.9％),RPL5 (7.1％) and RPL35a(4.8％).The median onset hemoglobin level was 42.5 g/L.A total of 12 patients had physical malformation,with the most common on heart and fingers.A total of 37 patients received hormone therapy,and the total initial response rate was 89.2％ (33/37 cases).One of the patients with hormone inefficiency was treated successfully with cyclosporin A,and the other 3 patients were treated with blood transfusion.Conclusions RPS19 was the most common gene mutation in DBApatients.Most of the RPS17 mutations were copy number variation.The deletion of large fragments should be paid more attention to in the detection of DBA genetic analysis.Patients with RPL5 mutation showed more malformation than other groups.No significant difference was found in terms of age of onset,hemoglobin level of onset,incidence of malformation and effective rate of hormone treatment in each group.

Objective:To investigate the effects of hemophagocytic syndrome also known as hemophagocytic lymphohistiocytosis (HLH) on the clinical features and therapeutic efficacy of patients with Epstein-Barr virus-positive T-cell lymphoma (EBV-TCL).Methods:The clinical data of patients with EBV-TCL diagnosed by pathological examination in the First Affiliated Hospital of Guangzhou Medical University from November 2015 to August 2020 were retrospectively analyzed. According to whether they were accompanied with HLH at the time of onset, patients were divided into HLH group (10 cases) and non-HLH group (13 cases), and the clinical features and prognosis of the two groups were compared. The curative effects of different treatment methods and patients with different plasma EBV-DNA titers were compared.Results:Among 23 patients, 3 cases (13.0%) were in Ann Arbor stage Ⅰ-Ⅱ, 20 cases (87.0%) were in stage Ⅲ-Ⅳ; the International Prognostic Index (IPI) score was 1 point in 3 cases (13.0%), 2 points in 4 cases (17.4%), 3 points in 8 cases (34.8%), 4 points in 8 cases (34.8%). In the HLH group, there were 2 cases of aggressive NK-cell leukemia and 3 cases of childhood systemic EBV-TCL. There were no cases of above two pathological types in the non-HLH group. In the HLH group, the proportions of patients with fever, bone marrow invasion, IPI score > 2 points, and EBV-DNA > 10 4 copies/ml were higher than those in the non-HLH group (all P < 0.05). The objective response rate (complete remission plus partial remission) of all patients after chemotherapy was 47.8% (11/23); there were 3 cases undergoing hematopoietic stem cell transplantation in both the HLH group and the non-HLH group, and all achieved objective remission. The objective remission of 7 patients and 10 patients who did not undergo hematopoietic stem cell transplantation in the HLH group and non-HLH group after lymphoma chemotherapy had 0 case and 5 cases, respectively, and the difference was statistically significant ( P = 0.044). In the chemotherapy alone group, 5 of 17 patients had objective remission, 6 patients in the chemotherapy plus transplantation group had objective remission, and the difference was statistically significant ( P = 0.039). Among 16 patients whose plasma EBV-DNA titers turned negative, 11 patients had objective remission, and 7 patients whose plasma EBV-DNA titers were continuously positive had no objective remission, and the difference was statistically significant ( P = 0.001). The 1-year overall survival rate of all patients was 69.3%, and the 2-year overall survival rate was 52.0%. In the HLH group, the 1-year and 2-year overall survival rates of 7 patients receiving chemotherapy alone and 3 patients receiving chemotherapy plus transplantation were 42.9% and 66.7%, respectively. In the non-HLH group, the 1-year overall survival rates of 10 patients receiving chemotherapy alone and 3 patients receiving chemotherapy plus transplantation were 80.0% and 100.0%, respectively; the 2-year overall survival rates were 26.7% and 100.0%,respectively. The overall survival of patients receiving chemotherapy plus transplantation was better than that of those receiving chemotherapy alone in both the HLH group and the non-HLH group, and differences were statistically significant (all P < 0.05). Conclusions:The general clinical stage of patients with EBV-TCL is later, and the prognosis of EBV-TCL patients with HLH is worse. The therapeutic efficacy may be related to plasma EBV-DNA titers. Hematopoietic stem cell transplantation can improve the remission rate.

Dirofilaria immitis (heartworm) infections affect domestic dogs, cats, and various wild mammals with increasing incidence in temperate and tropical areas. More sensitive antibody detection methodologies are required to diagnose asymptomatic dirofilariasis with low worm burdens. Applying current transcriptomic technologies would be useful to discover potential diagnostic markers for D. immitis infection. A filarial homologue of the mammalian translationally controlled tumor protein (TCTP) was initially identified by screening the assembled transcriptome of D. immitis (DiTCTP). A BLAST analysis suggested that the DiTCTP gene shared the highest similarity with TCTP from Loa loa at protein level (97%). A histidine-tagged recombinant DiTCTP protein (rDiTCTP) of 40 kDa expressed in Escherichia coli BL21 (DE3) showed immunoreactivity with serum from a dog experimentally infected with heartworms. Localization studies illustrated the ubiquitous presence of rDiTCTP protein in the lateral hypodermal chords, dorsal hypodermal chord, muscle, intestine, and uterus in female adult worms. Further studies on D. immitis-derived TCTP are warranted to assess whether this filarial protein could be used for a diagnostic purpose.
Animal Structures/chemistry ; Animals ; Antibodies, Helminth/blood ; Antigens, Helminth/chemistry/*genetics/immunology/*isolation & purification ; Cloning, Molecular ; Dirofilaria immitis/chemistry/*genetics/immunology ; Disease Models, Animal ; Dogs ; Escherichia coli/genetics ; Gene Expression ; Molecular Sequence Data ; Molecular Weight ; Recombinant Fusion Proteins/chemistry/genetics/immunology/isolation & purification ; Sequence Analysis, DNA ; Tumor Markers, Biological/chemistry/*genetics/immunology/*isolation & purification